Psychosocial hypertension develops in mice that compete in groups of 32 males and females in complex population cages (Circ Res: 36, 156-164, 1975). At first reversible it gradually becomes fixed. Progressive arteriosclerosis leads to myocardial fibrosis and also interstitial nephritis, a modest percentage terminating in uremia at 6-9 months. In six colonies in which standard brew tea or coffee replaced the drinking water this deterioration was speeded to 5 months and the incidence of renal failure more than doubled. Social stress appears a critical co-factor since orderly control groups were unaffected by the beverage. A relationship between caffeine intake/kg/diem to blood urea and renal damage score at autopsy is beginning to take shape. It will be completed using colonies fed caffeine in water at strengths set to bracket a suspected breakpoint at the human equivalent of 10 mg/kg/diem. Conflict stressed colonies on water and non-stressed groups on caffeine will be controls. Plasma renin is elevated in early colonies but subsides after several weeks. This suggests a role in early but not late psychosocial hypertension. Blood pressure, caffeine, catecholamines, corticosterone and adrenal medullary catecholamine synthesizing enzymes will be studied at different stages in colony life. A magnetic tracking device will measure appropriate social behavioral variables of up to eight animals. By independently varying caffeine and psychosocial stress in a non-smoking population we will evaluate the hypothesis that they are synergistic in accelerating arteriosclerotic deterioration. The role of caffeine and behavior in the development of high- as opposed to low-renin hypertension will be studied.